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- Title
Altered GABA Receptor Expression and Seizure Threshold Following Acute Ethanol Challenge in Mice Lacking the RIIβ Subunit of PKA.
- Authors
Carlson, Stephen; O'Buckley, Todd; Thomas, Rhiannon; Thiele, Todd; Morrow, A.
- Abstract
Ethanol causes pathological changes in GABA receptor trafficking and function. These changes are mediated in part by ethanol activation of protein kinase A (PKA). The current study investigated the expression of the GABA α1 and α4 subunits and the kinase anchoring protein AKAP150, as well as bicuculline-induced seizure threshold, at baseline and following acute injection of ethanol (3.5 g/kg IP) in a mouse line lacking the regulatory RIIβ subunit of PKA. Whole cerebral cortices were harvested at baseline, 1 h, or 46 h following injection of ethanol or saline and subjected to fractionation and western blot analysis. Knockout (RIIβ−/−) mice had similar baseline levels of PKA RIIα and GABA α1 and α4 subunits compared to wild type (RIIβ+/+) littermates, but had deficits in AKAP150. GABA α1 subunit levels were decreased in the P2 fraction of RIIβ−/−, but not RIIβ+/+, mice following 1 h ethanol, an effect that was driven by decreased α1 expression in the synaptic fraction. GABA α4 subunits in the P2 fraction were not affected by 1 h ethanol; however, synaptic α4 subunit expression was increased in RIIβ+/+, but not RIIβ−/− mice, while extrasynaptic α4 and δ subunit expression were decreased in RIIβ−/−, but not RIIβ+/+ mice. Finally, RIIβ knockout was protective against bicuculline-induced seizure susceptibility. Overall, the results suggest that PKA has differential roles in regulating GABA receptor subunits. PKA may protect against ethanol-induced deficits in synaptic α1 and extrasynaptic α4 receptors, but may facilitate the increase of synaptic α4 receptors.
- Subjects
GABA receptors; CYCLIC-AMP-dependent protein kinase; GENE expression; ETHANOL; BICUCULLINE; SPASMS; LABORATORY mice; THERAPEUTICS
- Publication
Neurochemical Research, 2014, Vol 39, Issue 6, p1079
- ISSN
0364-3190
- Publication type
Article
- DOI
10.1007/s11064-013-1167-0